The use of DBS to treat movement disorders could be improved if i) there existed a more efficient and less intrusive means of delivering power wirelessly, ii) the probes had improved therapy localization and functionality (e.g. multiple, independently addressable electrodes), and iii) feedback to monitor electromodulation therapy and provide data for improved stimulation parameters. Ferro Solutions has demonstrated wireless power transfer from an external coil to a small magnetostrictive/electroactive (ME) receiver that is more efficient than coil-to-coil wireless power transfer currently used. ME receivers generate 3-5 W of power per cm3 of active ME material and are typically small enough (<0.1 cm3) to be easily implanted. Further, it has been demonstrated that the ME can transfer data wirelessly to the external coil at kbits/s rates. Dramatic advances have been made in the use of optically excited receptors, expressed in specifically selected neurons, to achieve more-highly-localized and functional DBS. Light is delivered via optical fibers to a region of the brain where therapy is required, but only neurons expressing the receptor proteins are stimulated. The program objective is to develop of a wireless, optical DBS system containing a miniature ME-based, wireless power receiver, energy storage and circuit for power conditioning/management, optical pulse-generation, and data communication as described in the body of the proposal). The enhanced localization afforded by the receptor-targeted optical DBS method will advance current understanding of the mechanisms and pathways of DBS, ultimately leading to more effective therapies for innumerable, neurologically-based disorders. Phase I of the program will involve optimization and further miniaturization of the ME receivers, development of circuits to condition the power for storage and or immediate delivery to the LED in the form of a predetermined pulse train appropriate for the intended stimulation. Preliminary studies on mice to identify more clearly the effective pathways and optical stimulus parameters will be conducted. The aim in Phase I is to demonstrate three critical competencies:1) effective wireless delivery of adequate power for optical neurostimulation at short external field duty cycles, 2) show the feasibility of delivering motion-control therapy by optical rather than electrical neurostimulation in mouse subjects, and 3) demonstrate the increased localization of DBS therapy by receptor-targeted optical neurostimulation. Phase II will focus on 1) integrating the energy storage cell with the ME transceiver and IC, 2) use of multiple, independently activated optical DBS probes, 3) expanding the number and understanding of optical receptor proteins, 4) refining optical pulse patterns for most effective neurostimulation, 5) gleaning new information about mechanisms and pathways of neurostimulation, and 6) packaging the system components for easy implanted beneath the scalp. 1 PUBLIC HEALTH RELEVANCE: The specific focus of this proposal is to simplify the delivery of DBS by more efficient wireless power transfer so that the power receiver can be in or on the skull, elimination of IPG in the thorax and elimination of long leads to the implanted electrode. Also, the neurostimulation will not be carried out electrically (which has poor localization) but rather by means of delivery of light through an optical fiber to the relevant region of the brain where selected neurons have expressed channelrhodopsin-2 so that they can be optically stimulated.